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Effects of interleukin-3 after chemotherapy for advanced ovarian cancer
B Biesma, PH Willemse, NH Mulder, DT Sleijfer, JA Gietema, R Mull, PC Limburg, J Bouma, E Vellenga and EG de Vries
Department of Internal Medicine, University Hospital Groningen, The
Netherlands.
To define the maximum tolerated dose and to study whether recombinant human
interleukin-3 (rhIL-3) reduced chemotherapy-induced neutropenia and
thrombocytopenia, 20 chemotherapy-naive patients with advanced ovarian
cancer eligible for treatment with 6 cycles of carboplatin-
cyclophosphamide every 4 weeks (day 1) were entered in a phase I/II open,
single-center trial. Cohorts of five patients received during 7 days 1, 5,
10, or 15 micrograms/kg/d rhIL-3 (days 5 through 11) in cycles 1, 3, and 5
by continuous intravenous (IV) infusion or once daily subcutaneous (SC)
administration. In control cycles 2, 4, and 6, no rhIL-3 was administered.
rhIL-3 significantly increased the recovery of leukocyte, neutrophil, and
platelet counts, especially at 5, 10, and 15 micrograms/kg rhIL-3. rhIL-3
also increased basophil, eosinophil, monocyte, and lymphocyte counts at
this dose steps. Effects on reticulocytes were limited. No difference in
efficacy between SC and IV rhIL-3 treatment was found. Chemotherapy
postponement for insufficient bone marrow recovery was necessary in 22 of
45 control cycles versus 2 of 49 rhIL-3 cycles (P less than .001). Platelet
transfusions were required in 7 of 45 control cycles versus 3 of 50 rhIL-3
cycles (P less than .5). rhIL-3 up to 10 micrograms/kg/d could be
administered without severe side effects. At 15 micrograms/kg/d, rhIL-3
headache was dose- limiting. Other side effects were fever, flu-like
symptoms, nausea, skin rash, flushing, facial erythema, and urticaria.
Liver toxicity occurred in rhIL-3 and control cycles. rhIL-3 slightly
increased tumor necrosis factor alpha, C-reactive protein, and serum
amyloid A plasma levels, whereas no effect on IL-6 plasma levels was
observed. rhIL-3 administered SC appears to be an interesting hematopoietic
growth factor for reduction of chemotherapy-induced myelotoxicity.
Volume 80,
Issue 5,
pp. 1141-1148,
09/01/1992
Copyright © 1992 by The American Society of Hematology
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